New Research Clarifies How SSRIs Work

A research study published in Nature this week expands our understanding of how exactly SSRIs (selective serotonin reuptake inhibitors) work. Nature.com has two articles up:

(1) The scientific journal article, “X-ray structures and mechanism of the human serotonin transporter”, by Jonathan A. Coleman, Evan M. Green and Eric Gouaux. This piece is geared toward scientists and specialists; most of us won’t understand it. You can read the one-paragraph abstract for free, but the full text is available only to subscribers.

(2) A popular science article, “Mysterious antidepressant target reveals its shape”, summarizing the research for interested laypeople. Most of us should stick with this article.

SSRIs are a class of drugs widely prescribed for depression, including Celexa, Lexapro, Prozac, Paxil, Zoloft and their generic equivalents. Despite their popularity, scientists don’t fully understand how SSRIs work. This new research helps clear up that mystery. From the second Nature article:

[SSRIs] address one hallmark of depression: low levels of the molecule serotonin, which neurons use to signal one another. By preventing a protein called serotonin transporter (SERT) form absorbing the serotonin back into neurons that release it, the drugs boost serotonin levels in the junctions between cells.

But the details of this mechanism have long eluded researchers, who have sought to crystallize and visualize the SERT protein since the early 1990s. […] Gouaux and his colleagues finally succeeded by creating small mutations in the SERT gene to make the protein more stable.

This article mentions similar research on the neurotransmitters dopamine and norepinephrine.

Debates continue over whether and how much “serotonin imbalance” causes depression. Continuing research may give us more objective, empirical answers to those questions. It may explain why antidepressants work better for some depression sufferers than others. It may allow more targeted, individualized drug treatements in the future.

This article mentions one much less encouraging trend:

Over the past decade, most major pharmaceutical companies have ceased research into and development of new psychiatric drugs — a task that has proven to be complicated, expensive and fruitless.

So it may be a while before new research translates into more effective drug treaments. Still, I’m hopeful for the future and extremely grateful to the researchers working on these questions.

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